Genetics: Understanding the genetic risk factors for COVID-19

A global effort to map the genetic underpinnings of SARS-CoV-2 infection and COVID-19 disease severity in humans has identified 13 new genomic regions associated with susceptibility and severity. An analysis of almost 50,000 patients with COVID-19 from 46 studies across 19 countries is reported in Nature. The ongoing investigations may provide new insights into how infection causes disease and could identify targets for drug development or repurposing.

Being male and increasing weight and age have been shown to contribute to disease severity in patients with COVID-19, but these risk factors alone do not explain the variability in disease severity. Host genetics have been shown to have an important role in the susceptibility and severity of infectious diseases, including respiratory viruses. To explore the role of human genetics in SARS-CoV-2 infection and COVID-19, the COVID-19 Host Genetics Initiative (COVID-19 HGI) formed an international network of researchers to collect, share and analyse data.

Genome-wide association meta-analyses in patients with COVID-19 from these studies reveals novel loci that are associated with SARS-CoV-2 infection or COVID-19 severity. The authors find overlap between some of the loci identified here and those previously associated with autoimmune or inflammatory diseases, or lung disease traits. Some of the loci were only found in distinct subpopulations; for example, two loci associated with disease severity were discovered in four studies of individuals with East Asian ancestry, highlighting the value of globally comprehensive analyses of individuals from diverse ancestries. This international collaboration has enabled the identification of novel host genetic factors associated with COVID-19 with unprecedented speed, the authors conclude, and continues to collect data to expand the analysis both in terms of size and in terms of diversity of ancestries included.